By Dr Giselle Roberts
Bone cancer. It’s not something you think about when you are a teenager. But for most osteosarcoma patients, the inevitable teenage growth spurt coincides with tumours developing in the bones around the knee, or the upper arm bone close to the shoulder.
Up to thirty Australians under the age of 19 are diagnosed with osteosarcoma each year. What’s more, it is incredibly difficult to treat: over one third of patients fail to respond to current therapies.
Dr Christine Hawkins, an expert on anti-cancer drugs, is investigating the best treatment options for humans… and their canine companions.
GISELLE ROBERTS: Chris, you specialise in researching the best treatment options for people diagnosed with osteosarcoma. I imagine there are particular challenges associated with this type of cancer, given its prevalence among teenagers.
CHRISTINE HAWKINS: Developing cancer in early life results in a more significant burden of disease. Osteosarcoma patients often present with a lump in the bone that might be initially disregarded as a sports injury or growing pain. By the time a diagnosis is made, the cancer may have spread. Thanks to advances in surgical techniques, amputation of an arm or a leg is often avoidable, but intensive chemotherapy is a probability.
GR: And with that comes another set of problems.
CH: Chemotherapy will eliminate osteosarcomas in about two thirds of patients, but those survivors will be left to contend with the effects of these drugs for the rest of their lives. There may be immediate side effects, such as nausea, fatigue and increased risk of infections and bleeding, but there are also other long-term effects.
GR: Like what?
CH: Two of the most life-threatening are heart damage and the formation of new cancers. We’re focussing on reducing the risk of patients developing these so-called therapy-related cancers. Chemotherapy works by damaging the DNA in tumour cells to induce cell death. Healthy cells also get exposed to these drugs, and can end up being mutated. These mutations can lead to new cancers arising months or years down the track. People have to focus on beating the first cancer, of course. But with improvements in therapy, particularly for cancers afflicting children and young adults, subsequent development of therapy-related cancers is becoming a real issue. This is compounded in cases of osteosarcoma, where a significant number of patients are also known to have difficulty repairing DNA damage. They have a high susceptibility to cancer and are more sensitive to the mutagenic effects of therapy.
GR: OK, so chemotherapy presents its own risks, but are there alternatives?
CH: Yes, and we are investigating candidate therapies that work in completely different ways to chemo. The first is a class of anti-cancer drugs called IAP antagonists. They deactivate IAP proteins present in osteosarcoma cells that contribute to their ability to grow and spread. The other class of drugs, called proteasome inhibitors, prevent proteins from being broken down and reused. In both cases, they show promising results.
GR: What I found particularly interesting is that while osteosarcoma might be rare in humans, it’s the most common primary bone tumour found in dogs. That led you to your current research around canine osteosarcoma?
CH: Yes. This type of cancer is really common in dogs, particularly in large breeds like greyhounds. Unfortunately, the prognosis is poor. Most dogs who get diagnosed with osteosarcoma die within a year. The age of cancer onset happens a little later than it does in humans, but otherwise there are striking similarities in disease progression. The current treatment options are also very similar – with the same classes of chemotherapy drugs used in both species, although amputation is still commonly used in dogs.
GR: Your new paper, published in Veterinary and Comparative Oncology, tests the ability of proteasome inhibitors to kill dog osteosarcoma cell lines.
CH: Our paper examines what doses of proteasome inhibitors are required to kill cells from canine and human osteosarcomas, and how we might use them in conjunction with existing treatment programs to optimise patient outcomes and minimise side effects.
GR: In a world where clinical trials for rare diseases are a funding and logistical challenge, this is a really exciting development for patients of all varieties.
CH: Part of the reason we do not have better treatment options for osteosarcoma is because it’s a rare cancer. Clinical trials are needed to test new therapies and, in this case, the human numbers are so low. Hundreds of patients are needed to complete a proper comparative study and trials need to involve numerous hospitals, which increases the complexity and cost. So, if we can find a treatment that works in dogs, there is a possibility it might work in humans too. The data might be enough to convince oncologists, hospitals, and drug companies to pursue other therapeutic options for the treatment of osteosarcoma.
GR: It’s win-win.
CH: We hope the end result will be better therapies for humans but, in the meantime, it is exciting to accomplish something that might help dogs and their owners. We need to cure more osteosarcoma patients, and they need safer treatment options that reduce the risk of therapy-related cancer. Hopefully we can make a difference in a tangible way.